rs10486547

Positions:

• chr7-27548587-G-A
• chr7-27548587-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152740.4(HIBADH):​c.485-5487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 152,138 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.038 (151 hom., cov: 31)
• Consequence: HIBADH NM_152740.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961

Genes affected

HIBADH (HGNC:4907): (3-hydroxyisobutyrate dehydrogenase) This gene encodes a mitochondrial 3-hydroxyisobutyrate dehydrogenase enzyme. The encoded protein plays a critical role in the catabolism of L-valine by catalyzing the oxidation of 3-hydroxyisobutyrate to methylmalonate semialdehyde. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIBADH	NM_152740.4	c.485-5487C>T		intron_variant		ENST00000265395.7
HIBADH	XM_047419834.1	c.182-5487C>T		intron_variant
HIBADH	XM_047419835.1	c.182-5487C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIBADH	ENST00000265395.7	c.485-5487C>T		intron_variant		1	NM_152740.4	P1
HIBADH	ENST00000425715.1	c.313-5487C>T		intron_variant		2
HIBADH	ENST00000428288.2	c.*204-5487C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5733 AN: 152020 Hom.: 151 Cov.: 31

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.00906

Gnomad SAS AF: 0.0747

Gnomad FIN AF: 0.00868

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0377 AC: 5735 AN: 152138 Hom.: 151 Cov.: 31 AF XY: 0.0374 AC XY: 2780 AN XY: 74370

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.00908

Gnomad4 SAS AF: 0.0743

Gnomad4 FIN AF: 0.00868

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0282 Hom.: 12

Bravo AF: 0.0371

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10486547; hg19: chr7-27588206;